Opioid analgesic dose and route conversion ratio studies: a scoping review to inform an eDelphi guideline.

BACKGROUND: Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries. Therefore, we performed a scoping systematic review of opioid conversion studies to inform an international eDelphi guideline. METHODS: To ensure a comprehensive review, we conducted a systematic search across multiple databases (OVID Medline, PsycINFO, Embase, EBM-Cochrane Database of Systematic Reviews and Registered Trials, LILACS, IMEMR, AIM, WPRIM) using studies published up to June 2022. Additionally, we performed hand and Google Scholar searches to verify the completeness of our findings. Our inclusion criteria encompassed randomized and non-randomized studies with no age limit, with only a few pediatric studies identified. We included studies on cancer, non-cancer, acute, and chronic pain. The level and grade of evidence were determined based on the Multinational Supportive Care in Cancer (MASCC) criteria. RESULTS: Our search yielded 21,118 abstracts, including 140 randomized (RCT) and 68 non-randomized (NRCT) clinical trials. We compared these results with recently published conversion ratios. Modest correlations were noted between published reviews and the present scoping systematic review. CONCLUSION: The present scoping systematic review found low-quality evidence to support an opioid conversion guideline. We will use these data, including conversion ratios and type and route of administration, to inform an eDelphi guideline.

The Burden of Protozoal and Helminth Intestinal Infections and Related Risk Factors Among the Households of Migrant Construction Workers in Bhopal.

There are a few existing gaps and paucity of literature from Southeast Asia on the prevalence of intestinal parasitic infections among migrant construction workers. The present cross-sectional study was conducted to address this gap among migrant construction workers and their households in Bhopal. The study design included an interview questionnaire survey prior to the enrollment of participants and stool sample collection. The stool samples were processed according to the study protocol of macroscopy, occult blood testing, microscopy techniques combined with modified acid-fast, and sedimentation techniques. Participants were deemed positive if they exhibited microscopic findings in one out of three stool samples per recruit. We recommended clinical consultation for these cases and provided a report. Direct therapeutic intervention was not part of the study. The total recruits were 361. The predominant age group was young, i.e., aged 21 to 30 years (122/361, 33.8%), with the majority of females (55.2%). Most workers were occupied with work of digging soil (47.4%). The majority of participants (93.1%) practiced open field defecation (OFD). The prevalence of intestinal parasitic infections among migrant workers and households was 36.9% (133/361). Monoinfection was 88.7%, with 41% from Entamoeba histolytica/Entamoeba dispar. Monoinfection with Hymenolepis nana (10.2%) was a predominant helminth. The most common coinfection observed was of Giardia intestinalis with Ancylostoma duodenale (26.7%). Hand washing was the only independent predictor with an odds ratio of 3.6. Migrant behavior of the construction workers and their households was the major reason for not reaching the benefits of deworming schemes for children and vulnerability to intestinal parasitic infections.

Conversion ratios: Why is it so challenging to construct opioid conversion tables?

Standardizing opioid management is challenging due to the absence of a ceiling dose, the unknown ideal therapeutic plasma level, and the lack of an clear relationship between dose and therapeutic response. Opioid rotation or conversion, which is switching from one opioid, route of administration, or both, to another, to improve therapeutic response and reduce toxicities, occurs in 20-40 percent of patients treated with opioids. Opioid conversion is often needed when there are adverse effects, toxicities, or inability to tolerate a certain opioid formulation. A majority of patients benefit from opioid conversion, leading to improved analgesia and less adverse effects. There are different published ways of converting opioids in the literature. This review of 20 years of literature is centered on opioid conversions and aims to discuss the complexity of converting opioids. We discuss study designs, outcomes and measures, pain phenotypes, patient characteristics, comparisons of equivalent doses between opioids, reconciling conversion ratios between opioids, routes, directional differences, half-lives and metabolites, interindividual variability, and comparison to package insert information. Palliative care specialists have not yet come to a consensus on the ideal opioid equianalgesic table; however, we discuss a recently updated table, based on retrospective evidence, that may serve as a gold standard for practical use in the palliative care population. More robust, well-designed studies are needed to validate and guide future opioid conversion data.

Inpatient Transition from Methadone to Buprenorphine-Naloxone Using a Microdosing Strategy in a Postoperative Cancer Patient: A Case Report.

Background: Buprenorphine initiation in opioid-tolerant patients usually requires decreasing the total opioid intake per day due to its potential for precipitating withdrawal. However, this strategy may not be tolerated in patients who require higher amounts of opioids, such as those with cancer pain. Case Presentation: We utilized a buprenorphine microdosing strategy for a postoperative cancer patient who was previously taking buprenorphine-naloxone for chronic noncancer pain, then initiated on methadone for uncontrolled cancer-related pain. He had a planned cancer resection in the hospital. He subsequently underwent a successful transition from methadone to buprenorphine-naloxone through microdosing in one week with close monitoring in the inpatient setting. Conclusions: Using a microdosing strategy to transition from methadone to buprenorphine-naloxone in a span of days was achieved in this case report. More research regarding the feasibility and tolerability of microinductions is needed, especially in the setting of chronic pain or cancer-related pain.

Midfacial toddler excoriation syndrome (MiTES): case series, diagnostic criteria and evidence for a pathogenic mechanism.

BACKGROUND: PRDM12 polyalanine tract expansions cause two different disorders: midfacial toddler excoriation syndrome (MiTES; itch with normal pain sensation associated with 18 homozygous alanines (18A); and congenital insensitivity to pain (CIP) with normal itch associated with 19 homozygous alanines (19A). Knowledge of the phenotype, genotype and disease mechanism of MiTES is incomplete. Why 18A vs. 19A PRDM12 can cause almost opposite phenotypes is unknown; no other polyalanine or polyglutamine tract expansion disease causes two such disparate phenotypes. OBJECTIVES: To assess the genotype and phenotype of nine new, nine atypical and six previously reported patients diagnosed with MiTES. METHODS: Using cell lines with homozygous PR domain zinc finger protein 12 (PRDM12) containing 12 alanines (12A; normal), 18A (MiTES) and 19A (CIP), we examined PRDM12 aggregation and subcellular localization by image-separation confocal microscopy and subcellular fractionation Western blotting. RESULTS: MiTES presents in the first year of life; in all cases the condition regresses over the first decade, leaving scarring. The MiTES phenotype is highly distinctive. Features overlapping with PRDM12 CIP are rarely found. The genotype-phenotype study of the PRDM12 polyalanine tract shows that having 7-15 alanines is normal; 16-18 alanines is associated with MiTES; 19 alanines leads to CIP; and no clinically atypical cases of MiTES had a polyalanine tract expansion. PRDM12 aggregation and subcellular localization differed significantly between 18A and normal 12A cell lines and between 18A and 19A cell lines. MiTES is a new protein-aggregation disease. CONCLUSIONS: We provide diagnostic criteria for MiTES and improved longitudinal data. MiTES and CIP are distinct phenotypes, despite their genotypes varying by a single alanine in the PRDM12 polyalanine tract. We found clear distinctions between the cellular phenotypes of normal, MiTES and CIP cells. We hypothesize that the developmental environment of the trigeminal ganglion is unique and critically sensitive to pre- and postnatal levels of PRDM12.

Midfacial toddler excoriation syndrome (MiTES) causes facial itching and scratching in babies during their first year of life. MiTES tends to improve over the time period of approximately 10 years, but it can leave scars. Congenital insensitivity to pain (CIP) is a condition where a person cannot feel pain and is present from birth. This study looked at two conditions: MiTES and CIP. We specifically investigated changes in a gene called PRDM12, focusing on a part of the gene called the polyalanine tract ­ a sequence of many alanines (alanine is a type of amino acid). We discovered that the normal range for this sequence is between 7 and 15 alanines. If there are 16 to 18 alanines, it is associated with MiTES and causes the PRDM12 protein to clump together inside the cell. However, if there are 19 alanines, it leads to CIP, and the PRDM12 protein clumps together and moves to the cytoplasm, where it should not be. We found new evidence to suggest that MiTES is a disease where proteins clump together. Overall, our study findings show that despite there only being a small change in the same gene, MiTES and CIP are very different conditions.

Dynamic intervention to enhance the stability of PEGylated Ibrutinib loaded lipidic nano-vesicular systems: transitioning from colloidal dispersion to lyophilized product.

Liposomes being a promising colloidal system facilitates delivery of drugs with limited pharmacokinetic properties to achieve desirable clinical applications. However, development of a stable liposomal system is always challenging due to multiple complexities involved. Aqueous instability of liposomes and impact of various process and formulation parameters can lead to serious alteration of its therapeutic performance. In the proposed work, the authors aim to develop stable Ibrutinib-loaded liposomes using lyophilization and Quality-by-Design and assess their long-term stability. Ibrutinib-loaded liposomes were developed and optimized using Quality-by-Design technique and were further PEGylated and characterized for the same. Effect of cryoprotectants during lyophilization and other parameters are evaluated to obtain a robust formulation. The stability studies were conducted upto 6 months at various storage conditions to evaluate the effect of lyophilization. The impact of formulation, processing and lyophilization parameters on physicochemical properties of developed liposomal systems were evaluated and are critically discussed. Liquid dispersion exhibited a %degradation of 16-36% at 25 °C/60% RH which was reduced for less than 1% in lyophilized formulation for 6 months. Critical analysis and assessment of various parameters lead to identification of optimum conditions to manufacture this drug product and also opens way forward for further evaluation and translational possibilities.

O-Glycome Profiling of Breast Cancer Cell Lines to Understand Breast Cancer Brain Metastasis.

Breast cancer is the second leading cause of cancer-related death among women and a major source of brain metastases. Despite the increasing incidence of brain metastasis from breast cancer, the underlying mechanisms remain poorly understood. Altered glycosylation is known to play a role in various diseases including cancer metastasis. However, profiling studies of O-glycans and their isomers in breast cancer brain metastasis (BCBM) are scarce. This study analyzed the expression of O-glycans and their isomers in human breast cancer cell lines (MDA-MB-231, MDA-MB-361, HTB131, and HTB22), a brain cancer cell line (CRL-1620), and a brain metastatic breast cancer cell line (MDA-MB-231BR) using nanoLC-MS/MS, identifying 27 O-glycan compositions. We observed significant upregulation in the expression of HexNAc1Hex1NeuAc2 and HexNAc2Hex3, whereas the expression of HexNAc1Hex1NeuAc1 was downregulated in MDA-MB-231BR compared to other cell lines. In our isomeric analysis, we observed notable alterations in the isomeric forms of the O-glycan structure HexNAc1Hex1NeuAc1 in a comparison of different cell lines. Our analysis of O-glycans and their isomers in cancer cells demonstrated that changes in their distribution can be related to the metastatic process. We believe that our investigation will contribute to an enhanced comprehension of the significance of O-glycans and their isomers in BCBM.

Chatbot Performance in Defining and Differentiating Palliative Care, Supportive Care, Hospice Care.

CONTEXT: Artificial intelligence (AI) chatbot platforms are increasingly used by patients as sources of information. However, there is limited data on the performance of these platforms, especially regarding palliative care terms. OBJECTIVES: We evaluated the accuracy, comprehensiveness, reliability, and readability of three AI platforms in defining and differentiating "palliative care," "supportive care," and "hospice care." METHODS: We asked ChatGPT, Microsoft Bing Chat, Google Bard to define and differentiate "palliative care," "supportive care," and "hospice care" and provide three references. Outputs were randomized and assessed by six blinded palliative care physicians using 0-10 scales (10 = best) for accuracy, comprehensiveness, and reliability. Readability was assessed using Flesch Kincaid Grade Level and Flesch Reading Ease scores. RESULTS: The mean (SD) accuracy scores for ChatGPT, Bard, and Bing Chat were 9.1 (1.3), 8.7 (1.5), and 8.2 (1.7), respectively; for comprehensiveness, the scores for the three platforms were 8.7 (1.5), 8.1 (1.9), and 5.6 (2.0), respectively; for reliability, the scores were 6.3 (2.5), 3.2 (3.1), and 7.1 (2.4), respectively. Despite generally high accuracy, we identified some major errors (e.g., Bard stated that supportive care had "the goal of prolonging life or even achieving a cure"). We found several major omissions, particularly with Bing Chat (e.g., no mention of interdisciplinary teams in palliative care or hospice care). References were often unreliable. Readability scores did not meet recommended levels for patient educational materials. CONCLUSION: We identified important concerns regarding the accuracy, comprehensiveness, reliability, and readability of outputs from AI platforms. Further research is needed to improve their performance.

Cholestatic Pruritus Mimicking a Cutaneous Drug Eruption.

Pruritus, colloquially known as itch, is a common clinical symptom seen in a variety of dermatological conditions and systemic disorders. Pruritus can broadly be classified into four categories: neuropathic, neurogenic/systemic, psychogenic, and pruritoceptive. Initial categorization depends on anatomical and pathophysiological aspects of presentation and is reflective of underlying etiology. We report a case of an 83-year-old man presenting with generalized pruritus secondary to cholestasis from bile duct malignancy. This case is notable for atypical presenting features, including a trunk eruption comprised of excoriated papules with onset following meloxicam initiation, mimicking a cutaneous adverse drug reaction. Providers should consider systemic etiologies of pruritus in patients presenting with cutaneous eruptions with atypical features. Accurate categorization of pruritus can facilitate treatment and/or additional investigation of systemic disease.